Doxycycline Use Associated with Higher Risk of Pregnancy Loss

Pregnancies with a first-trimester doxycycline fill had a 36% to 54% higher risk of ending in loss than those treated with amoxicillin, a macrolide for respiratory tract infections (RTIs), or clindamycin for acne, according to an analysis of more than 218,000 pregnancies published in Annals of Internal Medicine.¹

“The key message is that doctors should consider avoiding doxycycline in women of childbearing age who are not using reliable contraception, where suitable alternatives are available,” said Kelton Tremellen, PhD, gynecologist and professor at Flinders University, according to the Royal Australian College of General Practitioners.²

Researchers analyzed data across 2 massive database cohorts covering commercial MarketScan and Medicaid populations.^1,2

By using active comparator groups rather than unexposed controls, the investigators minimized confounding by underlying infection, revealing that first-trimester doxycycline fills for RTIs were associated with a 40% to 54% higher risk of pregnancy loss compared with amoxicillin and a 36% to 39% higher risk compared with macrolides. For acne indications, doxycycline exposure in commercial insurance claims was associated with a 49% increased risk compared with topical clindamycin.

Health experts note that this active-comparator design offers clinicians and dispensing pharmacists convincing population-level evidence that exposure with specific antibiotics in early gestation could pose distinct risks.²

READ MORE: COVID-19, Flu Shots Coadministered Are Well-Tolerated in Pregnancy

Evaluative Evidence Across Global Registries

Findings from the US dataset align with broader observational registry research conducted internationally, reinforcing concerns for pharmacy professionals. A Norwegian population-based registry study encompassing over 700,000 pregnancies demonstrated a 56% increased hazard of miscarriage among women exposed to doxycycline during early pregnancy.³

That investigation similarly highlighted that although first-line urinary tract and respiratory choices such as amoxicillin, nitrofurantoin, and pivmecillinam showed no association with pregnancy loss, less commonly used agents including doxycycline, metronidazole, and ciprofloxacin carried significantly elevated risks. Methodological adjustments for confounding by indication further indicate that despite underlying infection accounting for part of the observed risk, systemic antimicrobial choice remains a critical determinant of fetal safety during early organogenesis.

Pharmacists reviewing reproductive toxicity data must distinguish between spontaneous pregnancy loss and structural birth defects.⁴

A large population-based cohort study examining over 265,000 pregnancies in Israel found that first-trimester doxycycline exposure was not associated with an increased risk of total major congenital malformations or organ-specific structural anomalies up to 1 year of age. This critical nuance demonstrates that although doxycycline may not function as a classical teratogen causing structural malformations in surviving infants, its potential interference with early placental development elevates the probability of early gestational loss.^2,4

Clinical Practice and Pharmacy Stewardship Considerations

For community and health-system pharmacists, these findings carry profound clinical implications for medication therapy management and routine dispensing. Antibiotics represent nearly 80% of all prescription medications dispensed during pregnancy, with up to 25% of pregnant individuals receiving an antimicrobial agent.^3,5

Under the FDA’s Pregnancy and Lactation Labeling Rule, legacy letter categories have been replaced with comprehensive clinical summaries, placing greater responsibility on pharmacists to evaluate reproductive potential, pregnancy status, and drug-specific safety profiles prior to dispensing. Because a substantial proportion of pregnancies are unplanned, pharmacists serve as an essential safety checkpoint when evaluating antibiotic orders for women of childbearing age.^2,5

When filling prescriptions for conditions such as RTIs or acne in women of reproductive age, pharmacists should proactively screen for pregnancy status and contraception usage.

Where suitable alternatives exist, recommending safer therapeutic options such as amoxicillin, cephalosporins, or topical clindamycin can mitigate unnecessary fetal exposure. In instances where doxycycline remains clinically necessary, such as for specific tick-borne illnesses or severe resistant infections, pharmacists must collaborate with prescribers to weigh the immediate maternal therapeutic benefit against potential fetal risks.^2,3,5

By maintaining rigorous antimicrobial stewardship and patient-centered counseling, pharmacists play a pivotal role in optimizing infectious disease outcomes while protecting maternal and fetal health.⁵

“Doxycycline use for RTI or acne during early pregnancy was associated with an increased risk for pregnancy loss,” concluded authors of the current study.¹ “Clinicians may use this information to weigh risks and benefits when prescribing doxycycline to reproductive-aged women.”

READ MORE: Women’s Health Resource Center

REFERENCES

1. Winterstein AG, Chen HK, Thai T, et al. Doxycycline and risk for pregnancy loss. Ann Intern Med. November 9, 2026. doi:10.7326/annals-26-01647

2. Liotta M. Miscarriage risk from common antibiotic reaffirmed. Royal Australian College of General Practitioners. November 10, 2026. Accessed November 10, 2026. https://www1.racgp.org.au/newsgp/clinical/miscarriage-risk-from-common-antibiotic-reaffirmed

3. Boissiere-O'Neill T, van Gelder MMHJ, Engjom HM, et al. Exposure to systemic antimicrobials during pregnancy and risk of miscarriage: a population-based registry study. BJOG. 2026;133(7):1394-1404. doi:10.1111/1471-0528.18155

4. Shitrit IB, Idan D, Hasidim AA, et al. Doxycycline safety during pregnancy: a large population-based cohort of pregnancies. Infection. 2025;53(6):2739-2747. doi:10.1007/s15010-025-02622-9

5. Nguyen J, Madonia V, Bland CM, et al. A review of antibiotic safety in pregnancy-2025 update. Pharmacotherapy. 2025;45(4):227-237. doi:10.1002/phar.70010